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Biomedical subjects

R Balakrishnan

Publications and source records attributed to R Balakrishnan.

At least 37 records · Page 2Linked to original sources

An endoscopic approach to the deviated nasal septum--a preliminary study.

The authors have used the nasal endoscope for the precise identification of pathological abnormalities of the nasal septum in relation to the lateral nasal wall including the osteo-metal complex and in its ultraconservative management. The aim of the study was to compare the efficacies of endoscope-aided septoplasty (EAS) over traditional septoplasty (TS) in treating the pathological septum and turbinates, performed in 30 cases each. The subjective assessment was carried out by visual analogue scores and objective assessment by nasal endoscopy. This study demonstrates the superiority and limitations of the endoscopic approach in managing a deviated nasal septum and the turbinates. The endoscope-aided technique was found to be more effective in relieving the contact areas and nasal obstruction (p = < or = 0.05). The authors advocate a combined approach--an endoscopic approach for inaccessible posterior deviation and the conservative traditional technique for accessible anterior deviation of the nasal septum.

Adolescent↗

Alzheimer's beta-amyloid peptide: affinity for metal chelates.

Alzheimer's amyloid peptide, A beta(1-42) and its fragments, A beta(1-28) and A beta(1-16), were chromatographed on IDA-M(II) columns (M: Cu2+, Ni2+ and Zn2+). The retention of A beta(1-42) and its fragments on IDA-Cu(II) could not be reversed in decreasing a gradient of pH, from 7.0 to 4.0. All A beta peptides were recovered from IDA-Ni(II) columns in a decreasing pH gradient from 7.0 to 4.0, within the pH range from 5.6 to 5.1. A beta(1-42) peptide was strongly retained on IDA-Zn(II) at pH 4.0, but its A beta(1-28) and A beta(1-16) were only transiently retained on IDA-Zn(II) columns when applied at pH 6.1. We submit that histidine clusters, residing both in the Alzheimer's beta-amyloid peptide and in most of the APP/APLP superfamily of proteins, constitute high-affinity binding sites for immobilized metal chelates.

Alzheimer Disease↗

Paromomycin and geneticin inhibit intracellular Cryptosporidium parvum without trafficking through the host cell cytoplasm: implications for drug delivery.

Cryptosporidium parvum, which causes intractable diarrhea and lethal wasting in people with AIDS, occupies an unusual intracellular but extracytoplasmic niche. No reliable therapy for cryptosporidiosis exists, though the aminoglycoside paromomycin is somewhat effective. We report that paromomycin and the related compound geneticin manifest their major in vitro anti-C. parvum activity against intracellular parasites via a mechanism that does not require drug trafficking through the host cell cytoplasm. We used both normal and transformed aminoglycoside-resistant Caco-2 or MDBK cells in these studies. Timed-exposure experiments demonstrated that these drugs inhibit intracellular but not extracellular parasites. Apical but not basolateral exposure of infected cells to these drugs led to very significant parasite inhibition, indicating an apical topological restriction of action. We estimated intracytoplasmic concentrations of paromomycin, using an intracellular bacterial killing assay, and found that C. parvum infection did not lead to increased paromomycin concentrations compared to those in uninfected cells. Global [3H]paromomycin uptake by Caco-2 cells was approximately 200-fold higher than the estimated intracytoplasmic paromomycin concentration, suggestive of host cell vesicular uptake and concentration (as has been reported with other cell lines). However, preinfection exposure of Caco-2 cells to paromomycin did not result in subsequent inhibition of parasite development, indicating that if exogenous paromomycin enters the infected host cell vesicular compartment, it does not effectively communicate with the parasite. Thus, the apical membranes overlying the parasite and parasitophorous vacuole may be the unsuspected major route of entry for paromomycin and may be of importance in the design and discovery of novel drug therapies for the otherwise untreatable C. parvum.

Animals↗

Taste sensilla of flies: function, central neuronal projections, and development.

Taste sensilla of flies are composed of only a few cells, all of which have different functions. Depending on the species and on the sensillum type, there are from 2-5 neurons, each of which has its own stimulus specificity, and each of which makes a different contribution to the fly's behavior. In addition, taste sensilla include several nonneuronal cells that are important both for the development of the sensillum and for its functioning. The component cells of a sensillum derive from a single epidermal precursor according to a stereotyped sequence of mitoses. This review focuses on the different phenotypes of the component cells of taste sensilla, particularly the stimulus sensitivity and central neuronal anatomy of the receptor neurons, and on the development of this multicellular organ from a single precursor cell.

Animals↗

Crystal structures of the copper and nickel complexes of RNase A: metal-induced interprotein interactions and identification of a novel copper binding motif.

We report the crystal structures of the copper and nickel complexes of RNase A. The overall topology of these two complexes is similar to that of other RNase A structures. However, there are significant differences in the mode of binding of copper and nickel. There are two copper ions per molecule of the protein, but there is only one nickel ion per molecule of the protein. Significant changes occur in the interprotein interactions as a result of differences in the coordinating groups at the common binding site around His-105. Consequently, the copper- and nickel-ion-bound dimers of RNase A act as nucleation sites for generating different crystal lattices for the two complexes. A second copper ion is present at an active site residue His-119 for which all the ligands are from one molecule of the protein. At this second site, His-119 adopts an inactive conformation (B) induced by the copper. We have identified a novel copper binding motif involving the alpha-amino group and the N-terminal residues.

Binding Sites↗

Crystal structure of a dipeptide Boc-Aib-Phe-OMe.

In order to understand the effect of the restrictions posed by the Aib residue on peptide conformation we studied the crystal structure of a dipeptide tBoc-Aib-Phe-OMe. Crystals of this compound are triclinic, space group P1 with a = 9.600(1) A, b = 10.262(1) A, c = 10.799(1) A, alpha = 98.43 degrees (1), beta = 99.18 degrees (1), gamma = 98.87 degrees (1), V = 1021.69(18) A3 and Z = 2. The structure was solved by direct methods and refined to an R-factor of 4.98%. The backbone conformational angles for the Aib residue in molecule A are in the left-handed helical region, while in molecule B they are in the right-handed helical region. The Phe residue in molecule A is in the right-handed helical conformation, while in molecule B it is in the beta-region. The peptide units are trans and show significant deviation from planarity [(omega 1 = 166.67(5) degrees and omega 2 = -177.9(5)].

Amino Acid Sequence↗

The role of antennal sensory cues in female responses to courting males in the cricket Teleogryllus oceanicus

Courtship communication in the field cricket Teleogryllus oceanicus is multimodal, involving a minimum of both acoustic and chemical cues. The acoustic signal, or courtship song, is necessary to elicit normal levels of female mounting of the male during courtship. Antennal input is also crucial since antennectomized females show highly reduced levels of mounting. Immobilization of the scape&shy;pedicel and pedicel&shy;flagellum joints of female antennae had no effect on mounting probability, suggesting that mechanosensory input from chordotonal organs at the base of the antenna is not necessary. The antennal flagellum is a multimodal sensory organ, which contains both mechanoreceptors and chemoreceptors. In order to dissect the roles of different flagellar modalities, we treated antennae with zinc sulphate. This suppressed a well-characterized contact-chemosensory behaviour, initiation of courtship by males, and eliminated responsiveness of most chemosensory hairs as assayed electrophysiologically. Zinc sulphate treatment had no effect on a tactile antennal reflex, indicating that it selectively silenced chemoreceptors. Treatment of antennae with zinc sulphate reduced mounting levels nearly as much as antennectomy, suggesting that the main antennal cue required for the mounting responses is chemosensory, rather than mechanosensory, in nature.

Journal Article↗

Mutations in masquerade, a novel serine-protease-like molecule, affect axonal guidance and taste behavior in Drosophila.

The masquerade (mas) locus encodes an extracellular molecule with a striking similarity to serine proteases. The serine residue, which is essential for enzymatic activity, has been substituted by glycine, suggesting that MAS could serve to antagonize serine protease activity [Murugasu-Oei et al. (1995), Genes Dev. 9, 139-154]. We describe the expression pattern of mas mRNA and protein in the developing embryonic, larval and pupal nervous system and in the epidermis. Total loss of mas function is lethal and results in aberrations in the embryonic central and peripheral nervous systems, consistent with a role in axonal guidance. The possibility that the observed deficits in taste behavior, exhibited by animals with partial loss of mas function, are a result of defects in the adult brain are discussed.

Animals↗

A gene cassette for adapting Escherichia coli strains as hosts for att-Int-mediated rearrangement and pL expression vectors.

A cassette of genes from bacteriophage lambda, when carried on a derivative of bacteriophage Mu, renders strains of Escherichia coli (and in principle other Mu-sensitive bacteria) capable of supporting lambda-based expression vectors, such as rearrangement vectors and pL vectors. The gene cassette contains a temperature-sensitive allele of the repressor gene, cIts857, and a shortened leftward operon comprising, oLpL, N, xis and int. Transfection and lysogenization of this cassette into various host bacteria is mediated by phage Mu functions. Examples of regulated expression of the gene encoding T4 DNA ligase are presented.

Bacteriophage lambda↗

Foreign body in the ethmoid sinus.

An air gun pellet lodged in the posterior ethmoid sinus in a 1-year-old child is described. Functional endoscopic sinus surgery enabled the removal of the pellet, obviating an external ethmoidectomy.

Endoscopy↗

Appendix. Cloning and sequence of the gene encoding enzyme E-1 from the methionine salvage pathway of Klebsiella oxytoca.

The methionine salvage pathway converts the methylthioribose moiety of 5'-(methylthio)-adenosine to methionine via a series of biochemical steps. One enzyme active in this pathway, a bifunctional enolase-phosphatase called E-1 that promotes oxidative cleavage of the synthetic substrate 2,3-diketo-1-phosphohexane to 2-keto-pentanoate, has been purified from Klebsiella pneumoniae and is characterized in the preceding paper (Myers, R., Wray, J., Fish, S., and Abeles, R. H. (1993) J. Biol. Chem. 268, 24785-24791). We synthesized degenerate oligonucleotides corresponding to portions of the amino terminus of E-1. These oligonucleotides were used as polymerase chain reaction primers on whole genomic DNA from Klebsiella oxytoca. This resulted in an 82-base pair DNA fragment that was used as a hybridization probe to obtain a clone of the E-1 gene from a K. oxytoca gene library. The DNA sequence of the E-1 coding region was determined, and the amino acid sequence of E-1 was deduced. E-1 appears to represent a novel class of enzymes since no homology to known enzymes was found. Cloning the gene from K. oxytoca on a multicopy plasmid leads to overproduction of E-1 enzyme that has properties indistinguishable from those of the enzyme from K. pneumoniae.

Amino Acid Sequence↗

Closely linked lesions in a region of the X chromosome affect central and peripheral steps in gustatory processing in Drosophila.

We have analyzed a set of closely linked mutations on the X chromosome of Drosophila that lead to defects in gustatory behavior. The mutations map to a small region of the X chromosome between 10E1-4. Two distinct complementation groups, gustB and gustD, map to the ends of this region. These groups show complex complementation patterns with the mutations gustC and GT-1, which also map to this region. We describe the behavioral and electrophysiological properties of the mutants. These mutations affect peripheral receptor properties as well as more central processing steps in the gustatory pathway.

Animals↗

The shaker and shaking-B genes specify elements in the processing of gustatory information in Drosophila melanogaster.

Mutations that affect the physiological properties of neurones or the development of neuronal circuits are likely to have profound effects on sensory and motor pathways. We have examined the effects of mutations in two loci--the Shaker complex and shaking-B-on the taste pathway of Drosophila melanogaster Meigen at the behavioural and electrophysiological levels. The Shaker locus encodes a variety of A-type potassium channels that are likely to be tissue- and stage-specific. Flies containing the different Shaker alleles examined exhibit a variety of defects in their gustatory responses to sucrose, NaCl and KCl. The firing patterns of the labellar chemosensory neurones in response to these stimuli are normal. This suggests that the channels encoded by the Shaker locus are probably not involved in taste transduction, but affect central gustatory circuits. The shaking-B locus affects neuronal connectivity, though its molecular nature is unknown. Mutants at this locus show increased thresholds for detection of sucrose and fructose and lack the attraction response to 0.1 mol l-1 sodium chloride that is exhibited by the wild-type fly.

Action Potentials↗